Nearly 20% of the 382 million adults with diabetes in the world live in India. Within the United States, the prevalence of diabetes among Asian Indians is nearly twice that of non-Hispanic whites. While the contribution of risk factors such as unhealthy diets and physical inactivity to the diabetes epidemic has been evaluated, less traditional exposures such as persistent organic pollutants (POPs) remain unexplored. Epidemiological studies conducted largely in high-income countries have suggested an association of POPs, particularly polychlorinated biphenyls (PCBs) and organochlorine (OC) pesticides, with diabetes. The few surveillance studies available in India have not reported a decline in POPs levels in human serum over the past 30 years; thus, India is considered a hot spot for POPs exposure. Further, the phenotype of diabetes in Asian Indians differs from that of other ethnicities: diabetes occurs at a lower BMI and beta cell function declines at an earlier stage relative to insulin resistance in Asian Indians. This is of particular interest in considerin the effects of POPs because animal studies suggest that these pollutants affect diabetes risk via action on beta cells. The CARRS (Centre for cArdiometabolic Risk Reduction in South-Asia) Study, an ongoing collaboration between Emory University, the Public Health Foundation of India, the Madras Diabetes Research Foundation, and the All India Institute of Medical Sciences, follows a representative cohort of 12,271 adults (= 20 years old) enrolled between 2010-2011 from two urban sites in India (Delhi and Chennai). Participants provided blood samples for diabetes ascertainment and biobanking. The proposed R21 will establish a CDC-standardized laboratory facility at Jawaharlal Nehru University (JNU) for the measurement of POPs in human serum, where CARRS samples can be analyzed in a nested, prospective case-control study of n=301 incident diabetes cases and n=602 age- and sex-matched normoglycemic controls. The specific aims are: 1) To cross-validate gas chromatography-mass spectrometry methods for measuring the 4 most biologically relevant PCBs (118, 138, 153, 180) and 7 OC pesticides (p,p'-DDT, o,p'-DDT, p,p'-DDE, o,p'-DDE, -HCH, TNC, HCB) in human serum (n=45 cases, n=45 controls) between Emory and JNU. 2) To estimate the association of these 4 PCBs and 7 OC pesticides with incident diabetes using a nested case-control study design in a prospective cohort of adults (n=301 cases, n=602 controls) from urban India. We will then explore: 2a) effect modification by central obesity (waist circumference) and 2b) mediation by insulin resistance (HOMA-IR) and beta cell function (HOMA-B). Completion of the proposed R21 will build laboratory capacity in India and uniquely position a team of diabetes and environmental pollutant experts in the United States and India to conduct the largest prospective analysis of the association between POPs and incident diabetes, furthering the world's understanding of the role of these pervasive exposures in the diabetes epidemic.